The typical naked mole rat lives 25 to 30 years, during which time it shows little decline in activity, bone health, reproductive capacity, and cognitive ability. What is the secret to this East African rodent’s long, healthy life? Scientists from the United States and Israel have found a clue. From infancy to old age, naked mole rats are blessed with large amounts of a protein essential for normal brain function. “Naked mole rats have the highest level of a growth factor called NRG-1 (neuregulin 1) in the cerebellum. Its levels are sustained throughout their life, from development through adulthood,” said Yael Edrey, doctoral student at The University of Texas Health Science Center San Antonio’s Barshop Institute for Longevity and Aging Studies. The Barshop Institute has the largest colony of naked mole rats in the U.S. — 2,000 rodents scampering around a network of tubes and cages in humid conditions that mimic their natural underground habitat. Edrey is the lead author of research that compared lifelong NRG-1 levels across seven species of rodents, from mice and guinea pigs to blind mole rats and Damaraland mole rats. NRG-1 levels were monitored in naked mole rats at different ages ranging from 1 day to 26 years. The other six rodent species have maximum life spans of three to 19 years. The cerebellum coordinates movements and maintains bodily equilibrium. The research team hypothesized that long-lived species would maintain higher levels of NRG-1 in this region of the brain, with simultaneous healthy activity levels. Among each of the species, the longest-lived members exhibited the highest lifelong levels of NRG-1. The naked mole rat had the most robust and enduring supply. “In both mice and in humans, NRG-1 levels go down with age,” Edrey said.

The naked mole rat, a curiously strange, hairless rodent, lives many years longer than any other mouse or rat. Scientists at The University of Texas (UT) Health Science Center San Antonio’s Barshop Institute of Longevity and Aging Studies continue to explore this mystery. On May 2, 2012, a Barshop Institute team reported that the naked mole rat’s cellular machines for protein disposal — called proteasome assemblies — differ in composition from those of other short-lived rodents. The study appeared in the journal PLoS ONE. This is the first report of the molecular mechanisms that underlie the naked mole rat’s superior ability to maintain protein integrity. “More effective removal of damaged proteins within the cell would enable the animal to be able to maintain good function and is likely to contribute to its excellent maintenance of good health well into its third decade of life,” said Rochelle Buffenstein, Ph.D., of the Barshop Institute. Dr. Buffenstein is a professor of physiology and cellular and structural biology in the School of Medicine at the UT Health Science Center. Dr. Buffenstein and her research team reported in 2009 that the naked mole rat maintains exceptional protein integrity throughout its long and healthy life. In the new study, the team found a greater number of proteasomes and higher protein-disposal activity in naked mole rat liver cells. The Barshop Institute scientists, including lead author Karl Rodriguez, Ph.D., postdoctoral fellow, and Yael Edrey, a graduate student, also found large numbers of immunoproteasomes in the liver cells — a bit of a surprise because these protein disposers, which remove antigens after presentation in the immune system, are more commonly found in the spleen and thymus.